ANTITUMOR AGENTS .111. NEW 4-HYDROXYLATED AND 4-HALOGENATED ANILINO DERIVATIVES OF 4'-DEMETHYLEPIPODOPHYLLOTOXIN AS POTENT INHIBITORS OF HUMAN DNA TOPOISOMERASE-II
ANTITUMOR AGENTS .111. NEW 4-HYDROXYLATED AND 4-HALOGENATED ANILINO DERIVATIVES OF 4'-DEMETHYLEPIPODOPHYLLOTOXIN AS POTENT INHIBITORS OF HUMAN DNA TOPOISOMERASE-II
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DOI：
10.1021/jm00167a013
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发表时间：
1990-05-01
影响因子：
7.3
通讯作者：
CHENG, YC
中科院分区：
文献类型：
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作者：
LEE, KH;BEERS, SA;CHENG, YC
合成了一系列表鬼臼毒素或4‘-去甲基鬼臼毒素的C-4羟基化和卤代苯胺衍生物，并评价了它们对人DNA拓扑异构酶II的抑制活性和引起细胞蛋白连接DNA断裂的活性。化合物11-17和22在引起DNA断裂方面比依托泊苷更有效，而化合物11-13、15、16和20在抑制人DNA拓扑异构酶II方面与依托泊苷一样或更有活性。对KB细胞的细胞毒性似乎与它们抑制DNA拓扑异构酶II和引起细胞内蛋白质连接的DNA断裂的能力没有直接关系。
A series of C-4 hydroxylated and halogenated anilino derivatives of epipodophyllotoxin or 4''-demethylepipodophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 11-17 and 22 are more potent than etoposide in causing DNA breakage, while compounds 11-13, 15, 16, and 20 are as active or more active than etoposide in their inhibition of the human DNA topoisomerase II. The cytotoxicity in KB cells appears to have no direct correlation with their ability to inhibit DNA topoisomerase II and to cause protein-linked DNA breaks in cells.